南方医科大学学报2017，Vol.37Issue(10)：1283-1289,7.DOI:10.3969/j.issn.1673-4254.2017.10.01
iRGD靶向声学脂质体在类风湿关节炎诊疗中的作用
Efficacy of internalized RGD-modified echogenic liposomes in diagnosis and treatment in a mouse model of rheumatoid arthritis
摘要
Abstract
Objective To prepare internalized RGD (iRGD)-modified echogenic liposomes containing methotrexate (MTX) and indocyanine green (ICG) (iRGD-MTX-ICG-ELIP) and evaluate its targeting efficiency and inhibitory effect combined with ultrasound on synovial cells. Methods iRGD-MTX-ICG-ELIP was prepared by the thin-film rehydration and freeze-lyophilization method and its general characteristics and acoustic responsiveness were assessed. The targeting effect of the prepared liposome was observed by assessing its cell uptake in vitro.In a mouse model of rheumatiod arthritis,the targeting effect of the prepared liposome was determined by detecting the fluorescence intensity of the drug in arthrosis.The inhibitory effect of iRGD-MTX-ICG-ELIP combined with ultrasound on synovial MH7A cells in vitro were investigated using CCK8 test. Results The average diameter and zeta potential of iRGD-MTX-ICG-ELIP was 134.4 ± 17.61 nm and-10.07 ± 4.28 mV, and the entrapment efficiency of MTX and ICG was (62.56 ± 0.77)% and (95.13 ± 0.82)%, respectively. With ultrasound exposure, the release of MTX and ICG from iRGD-MTX-ICG-ELIP increased with the ultrasound intensity and with the exposure time. In HUVECs, the uptake efficiency of iRGD-MTX-ICG-ELIP was 1.89 times higher than that of non-targeted MTX-ICG-ELIP(P<0.05).In vivo imaging of mouse joint with rheumatiod arthritis showed that the fluorescence intensity of iRGD-MTX-ICG-ELIP was significantly stronger than that of the non-targeted liposome. CCK8 assay showed that iRGD-MTX-ICG-ELIP combined with ultrasound resulted in a survival rate of MH7A cells of (32.49±3.04)%, significantly lower than the rate of cells treated with iRGD-MTX-ICG-ELIP but without ultrasound(P<0.05).Conclusions iRGD-MTX-ICG-ELIP has a suitable particle size and can effectively target HUVECs and the joints with rheumatiod arthritis. With a good drug entrapment efficiency and acoustic responsiveness, the drug-loaded liposome shows enhanced inhibitory effect on MH7A cells combined with ultrasound in vitro, suggesting its potential in the treatment of rheumatoid arthritis.关键词
靶向给药/声学脂质体/超声释药/类风湿关节炎Key words
targeted drug delivery/echogenic liposomes/ultrasound triggered release/rheumatoid arthritis引用本文复制引用
甘珍,武昊,吴昊晗,周美君,严飞,刘红梅..iRGD靶向声学脂质体在类风湿关节炎诊疗中的作用[J].南方医科大学学报,2017,37(10):1283-1289,7.基金项目
国家自然科学基金(81571674,81771853) （81571674,81771853）
广州市科技计划(201607010115) （201607010115）
广东省自然科学基金(2014A030313341) Supported by National Natural Science Foundation of China(81571674, 81771853). （2014A030313341）
